Organ transplantation is a technique which has already been established as a final treatment for end-stage organ failure. From a medical standpoint, the greatest problem for organ transplantation is acute and chronic organ rejection. Clinically effective drugs which are currently in use include such powerful immunosuppressants as adrenocortical hormone, cyclosporin, tacrolimus, azathioprine, anti-thymocyte antibodies and the like. However, these drugs have a general depressant effect on the host's immune system. Such immunosuppression is usually a factor in the main causes of death following organ transplantation, including organ rejection, infection and malignant tumors. Therefore, it would seem that in addition to antigen-specific immunosuppression, safer and more successful transplantation could be achieved if immune tolerance was artificially introduced, making it possible for the organ to survive permanently with only initial treatment.
Moreover, the aforementioned immunosuppressants are also seen as promising prophylactic or therapeutic agents for auto-immune disorders such as rheumatism and psoriasis and allergic disorders such as allergic asthma (bronchial asthma and the like), allergic rhinitis, allergic conjunctivitis, allergic dermatitis (atopic dermatitis and the like) and pollinosis, or antirejection drug.
It has long been known that renal transplants are more successful in renal failure patients who receive repeated preoperative blood transfusions (Opelz G et al, Lancet 1, 696–698 (1974)). It has also been recognized that a more effective immune reaction is induced by allogeneic blood transfusion in which the transfusion is specifically matched to the donor (donor specific blood transfusion) (Opelz G et al, Transplant Proc 17, 2357–2361 (1985)) and verified by many experimental tests. In experiments with rodents, complete immune tolerance was induced in many cases through a single allogeneic blood transfusion (Marino H et al, Am J Surg 95, 267–273 (1958); Marquet et al, Transplant Proc III, 708–710 (1971); Fabre J W et al, Transplantation 14, 608–616 (1972)).
There have also been a variety of reports on the mechanism by which allogeneic blood transfusion might induce immune tolerance. Generally speaking, the mechanisms are depending on either cellular or humoral factors (Kobayashi, Eiji, Molecular Medicine 34, 796–804 (1997)). Clonal delation (Cranston D et al, Transplantation 42, 302–306 (1986)) and anergy (Dollman M J et al, J Exp Med 173, 79–87 (1991)) belong in the former mechanism, while the latter mechanism includes bioactive substances in vivo induced by allogeneic blood transfusion which are biologically active in vivo. One of humoral factors is anti-idiotype antibody, which has been shown to be produced immediately after allogeneic blood transfusion in animals (NagarkattI P S et al, Transplantation 36, 695–699 (1983); Downey W E III et al, Transplantation 49, 160–166 (1990); Baldwon W M III et al, Transplantation, 51, 481–485 (1991)) and humans (Horuzxko A et al, Immunology Letters 26, 127–130 (1990)), but less is known about the others.
And since bioactive substances derived through allogeneic transfusion which exhibit immunosuppression are endogenous substances, they can be expected to have fewer side effects than existing immunosuppressants.